Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide

Thomas C.T. Michaels, Andela Šarić, Samo Curk, Katja Bernfur, Paolo Arosio, Georg Meisl, Alexander J. Dear, Samuel I.A. Cohen, Christopher M. Dobson, Michele Vendruscolo, Sara Linse, Tuomas P.J. Knowles

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

66 Citeringar (SciVal)

Sammanfattning

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases. [Figure not available: see fulltext.].

Originalspråkengelska
Sidor (från-till)445-451
Antal sidor7
TidskriftNature Chemistry
Volym12
Utgåva5
DOI
StatusPublished - 2020

Ämnesklassifikation (UKÄ)

  • Läkemedelskemi

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